Role of deformable cancer cells on wall shear stress-associated-VEGF secretion by endothelium in microvasculature
Role of deformable cancer cells on wall shear stress-associated-VEGF secretion by endothelium in microvasculature
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DOI：
10.1371/journal.pone.0211418
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发表时间：
2019-02-22
期刊：
影响因子：
3.7
通讯作者：
Randles, Amanda
中科院分区：
文献类型：
--
作者：
Dabagh, Mahsa;Randles, Amanda
内皮表面层（糖萼）是肿瘤细胞粘附于内皮的主要生理调节因子。癌细胞表达血管内皮生长因子（VEGF），其通过降解糖萼来增加微血管壁的渗透性。也已经报道了在体外和体内，在暴露于> 0.6Pa的高壁剪切应力（WSS）下，内衬大动脉的内皮细胞显著介导VEGF表达。本研究的目的是探讨是否在迁移变形癌细胞附近的局部血流动力学条件可以影响微血管内皮细胞表达VEGF的功能。通过应用大规模并行血液动力学应用程序来模拟DCC和DCC周围流体之间的流体-结构相互作用，开发了毛细血管内迁移的可变形癌细胞（DCC）的三维模型。我们研究了DCC及其局部微环境之间的动态相互作用如何影响暴露在内皮上的WSS，在具有不同直径和流动条件的毛细血管的生理条件下。此外，我们量化了受DCC影响的内皮面积。我们的研究结果表明，DCC改变局部血流动力学在其附近的面积高达40倍的癌细胞侧表面。在该区域中，内皮经历0.6-12 Pa范围内的高WSS值。已经报道了暴露于该范围的WSS的内皮细胞表达VEGF。此外，我们证明了更硬的癌细胞在内皮上暴露更高的WSS。细胞刚度对其局部微环境的强烈影响是在直径
Endothelial surface layer (glycocalyx) is the major physiological regulator of tumor cell adhesion to endothelium. Cancer cells express vascular endothelial growth factor (VEGF) which increases the permeability of a microvessel wall by degrading glycocalyx. Endothelial cells lining large arteries have also been reported, in vitro and in vivo, to mediate VEGF expression significantly under exposure to high wall shear stress (WSS) > 0.6 Pa. The objective of the present study is to explore whether local hemodynamic conditions in the vicinity of a migrating deformable cancer cell can influence the function of endothelial cells to express VEGF within the microvasculature. A three-dimensional model of deformable cancer cells (DCCs) migrating within a capillary is developed by applying a massively parallel hemodynamics application to simulate the fluid-structure interaction between the DCC and fluid surrounding the DCC. We study how dynamic interactions between the DCC and its local microenvironment affect WSS exposed on endothelium, under physiological conditions of capillaries with different diameters and flow conditions. Moreover, we quantify the area of endothelium affected by the DCC. Our results show that the DCC alters local hemodynamics in its vicinity up to an area as large as 40 times the cancer cell lateral surface. In this area, endothelium experiences high WSS values in the range of 0.6-12 Pa. Endothelial cells exposed to this range of WSS have been reported to express VEGF. Furthermore, we demonstrate that stiffer cancer cells expose higher WSS on the endothelium. A strong impact of cell stiffness on its local microenvironment is observed in capillaries with diameters